Ferguson Kelly K, McElrath Thomas F, Mukherjee Bhramar, Loch-Caruso Rita, Meeker John D
University of Michigan School of Public Health, Department of Environmental Health Sciences, Ann Arbor, Michigan, United States of America.
Brigham and Women's Hospital, Harvard Medical School, Division of Maternal-Fetal Medicine, Boston, Massachusetts, United States of America.
PLoS One. 2015 Aug 28;10(8):e0135601. doi: 10.1371/journal.pone.0135601. eCollection 2015.
Phthalate exposure is prevalent in populations worldwide, including pregnant women. Maternal urinary metabolite concentrations have been associated with adverse reproductive outcomes, but underlying mechanisms remain unclear. Here we investigate inflammation as a possible pathway by examining phthalates in association with inflammation biomarkers, including C-reactive protein (CRP) and a panel of cytokines (IL-1β, IL-6, IL-10, and TNF-α) in a repeated measures analysis of pregnant women (N = 480). Urinary phthalate metabolites and plasma inflammation biomarkers were measured from samples collected at up to four visits per subject during gestation (median 10, 18, 26, and 35 weeks). Associations were examined using mixed models to account for within-individual correlation of measures. Few statistically significant associations or clear trends were observed, although in full models mono-carboxypropyl phthalate (MCPP) was significantly (percent change with interquartile range increase in exposure [%Δ] = 8.89, 95% confidence interval [CI] = 3.28, 14.8), and mono-benzyl phthalate (MBzP) was suggestively (%Δ = 6.79, 95%CI = -1.21, 15.4) associated with IL-6. Overall these findings show little evidence of an association between phthalate exposure and peripheral inflammation in pregnant women. To investigate inflammation as a mechanism of phthalate effects in humans, biomarkers from target tissues or fluids, though difficult to measure in large-scale studies, may be necessary to detect effects.
邻苯二甲酸盐暴露在全球人群中普遍存在，包括孕妇。孕妇尿液中的代谢物浓度与不良生殖结局有关，但其潜在机制仍不清楚。在此，我们通过在一项针对480名孕妇的重复测量分析中，研究邻苯二甲酸盐与炎症生物标志物（包括C反应蛋白（CRP）和一组细胞因子（IL-1β、IL-6、IL-10和TNF-α））之间的关系，来探究炎症是否是一条可能的途径。在孕期，每位受试者最多在四次访视时（中位数为10、18、26和35周）采集样本，测量尿液中的邻苯二甲酸盐代谢物和血浆炎症生物标志物。使用混合模型来检验相关性，以考虑测量值的个体内相关性。尽管在完整模型中，单羧丙基邻苯二甲酸盐（MCPP）与IL-6有显著相关性（暴露增加四分位间距时的百分比变化[％Δ] = 8.89，95％置信区间[CI] = 3.28，14.8），单苄基邻苯二甲酸盐（MBzP）与IL-6有提示性相关性（％Δ = 6.79，95％CI = -1.21，15.4），但观察到的统计学显著相关性或明显趋势较少。总体而言，这些发现几乎没有证据表明孕妇邻苯二甲酸盐暴露与外周炎症之间存在关联。为了研究炎症作为邻苯二甲酸盐对人类影响的一种机制，来自靶组织或体液的生物标志物，虽然在大规模研究中难以测量，但可能对于检测影响是必要的。
